Love it or hate it, doctors used to prescribe Marmite

Marmite is a savoury spread eaten on toast and sandwiches. It is made from concentrated yeast extract, manufactured from spent brewer’s yeast—a by-product of the beer brewing process.

Marmite became popular with the convergence of World War 1 and the discovery of vitamins in the early twentieth century. British troops carried Marmite in their ration packs as a source of B vitamins.

Then in the 1930s, medical researcher Lucy Wills made an intriguing observation. While in India, Wills studied a type of anaemia in pregnancy, then referred to as ‘pernicious anaemia of pregnancy.’ She noticed that economically disadvantaged women in Bombay were more prone to the condition, suggesting that the anaemia was probably some nutritional deficiency. Pure liver extracts (vitamin B12) treated true pernicious anaemia but did not reverse ‘pernicious anaemia of pregnancy.’ Wills speculated that there was some other nutritional factor missing. The mystery nutrient was known as the ‘Wills Factor’.

Lucy Wills then experimented on animals to find a dietary cure. She discovered that yeast extracts could prevent and cure the anaemia she was studying. And the cheapest source of this extract was Marmite.

Later, in the 1940s, the mystery ingredient that used to be known as the ‘Wills Factor’ was discovered to be folate (the natural form of folic acid). Marmite provides nearly 50% of the recommended daily allowance of folate per serving.

She was fit like a glove

It is logical for the reader to assume that surgical gloves were originally developed to prevent infection during surgery. However, the truth is that surgical gloves were adopted because Dr William Stewart Halsted took a keen interest in his head nurse, Miss Caroline Hampton.

Nurse Hampton suffered considerable skin irritation from the mercuric chloride solution used to disinfect her hands before surgery. As part of the standard antiseptic procedure at the hospital, she could not continue to work alongside Dr Halsted without dousing her hands in the corrosive chemical.

To ensure this “unusually efficient woman” remained in his operating room, Halsted made casts of her hands and asked the Goodyear Rubber Company to make two pairs of thin rubber gloves with gauntlets. The gloves, which could be sterilized by boiling, were the first rubber gloves ever used in a surgical operation.

They proved so effective in protecting nurse Hampton’s hands that Halsted’s assistants also started wearing them routinely. They also proved to be effective in advancing Dr Halsted’s romantic interests because he married nurse Hampton shortly afterwards.

Halsted himself, however, only used rubber gloves occasionally. Like most contemporary surgeons, he was convinced that gloves blunted his skill by interfering with his sense of touch.

Joseph Bloodgood, who trained under Halsted, started using rubber gloves for hernia operations and noticed fewer post-surgical infections in patients when the surgical team used gloves. After Bloodgood published his findings, surgeons began paying closer attention to the potential advantage of using gloves even though they still remained sceptical.

Dr Halsted, who had accidentally introduced rubber gloves into surgical practice, also helped pioneer local anaesthesia. He demonstrated that cocaine blocked nerve transmission, thereby laying the foundation for nerve block anaesthesia.

Like Sigmund Freud, his self-experimentation led to a cocaine addiction which he later replaced with a morphine addiction.

During his lifetime, Halsted had drawn his own blood to perform one of the earliest blood transfusions in the USA on his sister, who he later operated on. He also performed gallbladder surgery on his mother. Ironically, he ultimately died from complications of gallbladder surgery.

Blaming depression on a chemical imbalance in the brain?

How did doctors come to blame depression on brain chemicals?

The strange origin of this story lies in the roots of an Indian plant used by Mahatma Gandhi to treat his high blood pressure.

For centuries, traditional Ayurvedic medicine in India used the roots of a shrub called ‘Rauvolfia serpentina‘ (Indian snakeroot) to make Sarpagandha: a medicine that treated high blood pressure and mental illness.

Inspired by Ayurvedic practice, scientists extracted a chemical from the Indian snakeroot, developing one of the first drugs to treat hypertension. The drug was called reserpine.

In addition to its antihypertensive effect, reserpine also tranquillized horses and sedated excitable patients. And so, it also became one of the first antipsychotic drugs.

As more and more patients were prescribed reserpine for hypertension and schizophrenia, doctors noticed that some patients developed depression. When reserpine treatment was stopped and followed by rest or electric shock, the depression was reversed. Somehow, reserpine seemed to be causing depression.

Curiously, doctors noticed that patients being treated for tuberculosis (TB) became more joyful. These happy patients all took a drug designed to kill the bacteria causing tuberculosis. The name of that drug was iproniazid, and iproniazid–originally a TB drug–would become the world’s first antidepressant. [Iproniazid’s relationship to Nazi rockets is another story.]

The accidental effects of reserpine and iproniazid helped doctors stumble upon a revelatory theory. Reserpine made patients depressed. Iproniazid treated their depression. How did these findings relate to one another? What was the connection?

The solution to the problem lay in how these two drugs produce opposite effects on the brain’s chemistry.

Reserpine decreases the number of chemical messengers (called monoamine neurotransmitters) in the nervous system. On the other hand, iproniazid boosts the number of monoamine neurotransmitters.

Depression, doctors thought, was merely a lack of one or more monoamines. They called this theory “the monoamine hypothesis of depression.” Treating depression was thus possible by raising the concentrations of monoamines (e.g. noradrenaline, dopamine and serotonin). The monoamine hypothesis led to the development of new classes of drugs to treat mental illness.

We now know that the monoamine hypothesis has several shortcomings. Firstly, the observations related to reserpine were mostly erroneous. Certain drugs that boost monoamines are not antidepressants (e.g. cocaine), while other drugs that fail to increase monoamines are antidepressants (e.g. mianserin).

On top of that, the timing of the antidepressant drug effect and its therapeutic effect do not coincide. Antidepressants boost monoamines immediately, but the mood-enhancing effects in patients take weeks. The monoamine hypothesis theory subsequently became more elaborate and morphed into the ‘neurotransmitter receptor hypothesis of depression’. But that is yet another story.

How hives cured motion sickness

In 1947, Leslie Gay, an allergist working out of the Johns Hopkins’ allergy clinic, met with a woman who had broken out in hives.

Gay and his colleague, Paul Carliner, happened to be testing an experimental antihistamine drug at the time, and this patient with hives provided an opportunity for testing their new treatment. As a result, the woman received repeated doses of “Compound 1694”.

Her hives cleared up, but something else also happened.

The woman had suffered from motion sickness all her life. She arrived at her appointments feeling nauseous because she had to take the Monument Street trolley to reach the allergy clinic. However, she felt nausea-free when she rode the trolley home after her treatment.

Gay and Carliner recognized that they might be on to something. So, with the cooperation of bigwigs in the United States Army, they launched ‘Operation Seasickness’.

Operation Seasickness’ was an involuntary experiment using U.S. soldiers sailing to postwar Germany. Soldiers were either given the experimental drug (now called Dramamine) or a placebo. Soldiers who took the pill did not get seasick during the trip. Furthermore, soldiers who received a placebo, and suffered seasickness on the way to Germany, were cured when they took the experimental drug.

Shortly after that, Dramamine became available for public use. It is still used for motion sickness today.

Medical quacks

Quack is an abbreviation of quacksalver, an old word borrowed from the Dutch, kwakzalver. The term ‘quack’ meant ‘shouting’ in the Middle Ages so a kwakzalver was someone who shouted about salves; i.e., a “hawker of salve”. Quacksalvers sold their salves, oils and balms in marketplaces and at town fairs by loudly proclaiming the miraculous effects of their products.

Snake oil salesmen

When Chinese workers arrived in the United States to help build the Transcontinental Railroad in the 1800s, they brought their own traditional Chinese medicine to relieve pain and inflammation suffered from a long day’s work. Their remedy for treating arthritis and bursitis was to apply the oil from a Chinese water snake to aching body parts.

As the market boomed for Chinese water snake oil, entrepreneurs in the American Wild West looked for alternatives. It set the stage for the original snake oil salesman, a cowboy named Clark Stanley, “The Rattlesnake King”.

It was a time when pharmaceutical products were marketed on the back of ‘medicine shows’ involving live demonstrations, and at the 1893 World’s Columbian Exposition in Chicago, Stanley took the stage. He elaborately sliced open a live rattlesnake in true showmanship fashion, boiled the fat out of it, and deposited it in liniment jars he sold to spectators.

“Clark Stanley’s Snake Oil Treatment” was a hit with the crowd.

While Stanley recounted learning the secrets of snake oil from Hopi tribe medicine men in the Arizona desert, American doctors were less impressed.

Then the tide of public opinion slowly started turning. In 1905, Collier’s magazine called out fraudsters who sold poisonous products which pre-empted the Pure Food and Drug Act of 1907. Then, in 1917, a shipment of Clark Stanley’s Snake Oil Liniment was seized by the U.S. government. Scientists carefully analyzed the contents.

Clark Stanley’s Snake Oil did not contain any snake oil! Instead, investigators revealed the ingredients were a mixture of mineral oil, beef fat, red pepper, and turpentine. Stanley was fined for fraud.

Clark Stanley did not contest those charges. Having made his fortune, he was content to settle the fine and fade into history.

In fairness to the Chinese water snake oil, it probably did have therapeutic benefits due to the anti-inflammatory properties of its omega-3 fatty acid content.

Stressed to the nines

If cats only get nine lives, do classical music composers only get nine symphonies?

The “curse of the ninth” was a superstition created in the mind of the great composer Gustav Mahler. Mahler recognized that Beethoven, Schubert, Bruckner, and Dvořák had all died before completing a tenth symphony. As a result, Mahler was afraid that his ninth symphony would be his last.

Mahler had already written eight symphonies when personal tragedy inspired him to compose Das Lied von der Erde (“The Song of the Earth”). Afraid of invoking the curse of the ninth, Mahler refused to number this composition as a symphony. Instead, he subtitled the work: “A Symphony for Tenor, Alto (or Baritone) Voice and Orchestra.” Then, satisfied that he had escaped the curse, Mahler called his next symphony his ninth.

Fate, however, took little notice of Mahler’s wily tactics. Fulfilling his own superstitious prophecy, Gustav Mahler died before he could complete his tenth symphony.

Good deadside manner

Vladimir Bekhterev was a Russian neurologist who described 19 new diseases, including Bekhterev’s disease (ankylosing spondylitis), and 15 new reflexes. Bekhterev also revealed the role of the hippocampus in memory. His research laid the foundation to advance our knowledge in the fields of psychology and behaviourism.

His contribution to neuroscience was so significant that the German Professor of Anatomy, Friedrich Kopsch, remarked, “There are only two persons who know the anatomy of the brain perfectly—God and Bekhterev.”

Bekhterev died unexpectedly on December 24, 1927. Circumstances leading up to–and following– his death have been the subject of much speculation, shrouding it in mystery.

The day before his death, Bekhterev went to the Kremlin to examine Russian dictator Joseph Stalin. After consulting with Stalin, he returned to a medical congress and told colleagues: “I have just examined a paranoiac with a short, dry hand.” He was referring to Stalin’s disabled left arm.

The next day, Bekhterev was dead. Following his death, Stalin removed Bekhterev’s name from Soviet textbooks.

Did Joseph Stalin take offence to the doctor’s dismissive diagnosis and offhanded, unflattering description?

Stalin was known to doctor photos of himself to hide his physical imperfections. For example, in the famous photographic pose alongside Vladimir Lenin, photo technicians lengthened Stalin’s left arm and smoothed his skin blemishes caused by smallpox.

We will probably never know whether Vladimir Bekhterev’s insensitive communication caused his death the following day.

Waving the fag

During World War I, the commander of US forces, General John J “Black Jack” Pershing, was asked what he needed to win the war.

His reply: “You ask me what we need to win this war. I answer tobacco as much as bullets. Tobacco is as indispensable as the daily ration; we must have thousands of tons without delay.”

For decades to come, the First World War proved instrumental in entrenching the popularity of cigarettes.

British medical journal, ‘The Lancet’, expressed indifference at the time: “We may surely brush aside much prejudice against the use of tobacco when we consider what a source of comfort it is to the sailor and soldier engaged in a nerve-wracking campaign … tobacco must be a real solace and joy when he can find time for this well-earned indulgence”.

In 1917, the colourful inventor of corn flakes, John Harvey Kellogg, predicted that more American soldiers would be damaged by the cigarette than by German bullets.

Almost 100 years later, on March 14, 2014, Jonathan Woodson, US assistant secretary of defence for health affairs, issued the following memorandum:

“Prominence of tobacco products in [military] retail outlets, and permission for smoking breaks while on duty, sustain the perception that we are not serious about reducing the use of tobacco”.

Hot Docs

The annual Nathan’s Hot Dog Eating Contest started as a publicity stunt promoting Nathan’s Famous Hot Dogs. But it wasn’t the first successful marketing gimmick hatched by the company.

When co-founder Nathan Handwerker launched into the hot dog business with his wife in 1916, he set his price for a hot dog at five cents. Competitors were selling theirs at ten cents, creating the impression that Nathan’s food was low quality.

To change public perception, Nathan hired ordinary people—dressed them up in white coats and stethoscopes—and instructed them to eat hot dogs while stationed in front of his stand.

Hungry passers-by would see these ‘doctors’ munching on Nathan’s five-cent hot dogs and figured the cheap hot dogs must be healthy. Business boomed shortly afterwards.